Case Report: When Arteries Betray: Massive Post-transplantation Hemorrhage.

Hepatic artery pseudoaneurysm is a rare complication that may occur in the setting of liver transplantation and other traumatic instrumentation of the hepatobiliary system. This condition poses a significant morbidity and mortality risk and must be diagnosed and intervened upon emergently. Herein we present a case of hepatic artery pseudoaneurysm complicated by hemorrhagic shock in the setting of a post-liver transplant biliary leak. In this case, the patient was ultimately diagnosed via hepatic angiogram, treated with hepatic artery embolization, and required subsequent retransplantation. The objective of this case was to demonstrate the importance of maintaining a high clinical suspicion for hepatic artery pseudoaneurysm in the post-transplant setting, emphasize the use of computed tomography angiography as a primary diagnostic tool, and involving interventional radiology early in the treatment course.

Performance of AI-Enabled Electrocardiogram in the Prediction of Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND AND AIMS: Accessible noninvasive screening tools for metabolic dysfunction-associated steatotic liver disease (MASLD) are needed. We aim to explore the performance of a deep learning-based artificial intelligence (AI) model in distinguishing the presence of MASLD using 12-lead electrocardiogram (ECG). METHODS: This is a retrospective study of adults diagnosed with MASLD in Olmsted County, Minnesota, between 1996 and 2019. Both cases and controls had ECGs performed within 6 years before and 1 year after study entry. An AI-based ECG model using a convolutional neural network was trained, validated, and tested in 70%, 10%, and 20% of the cohort, respectively. External validation was performed in an independent cohort from Mayo Clinic Enterprise. The primary outcome was the performance of ECG to identify MASLD, alone or when added to clinical parameters. RESULTS: A total of 3468 MASLD cases and 25,407 controls were identified. The AI-ECG model predicted the presence of MASLD with an area under the curve (AUC) of 0.69 (original cohort) and 0.62 (validation cohort). The performance was similar or superior to age- and sex-adjusted models using body mass index (AUC, 0.71), presence of diabetes, hypertension or hyperlipidemia (AUC, 0.68), or diabetes alone (AUC, 0.66). The model combining ECG, age, sex, body mass index, diabetes, and alanine aminotransferase had the highest AUC: 0.76 (original) and 0.72 (validation). CONCLUSIONS: This is a proof-of-concept study that an AI-based ECG model can detect MASLD with a comparable or superior performance as compared with the models using a single clinical parameter but not superior to the combination of clinical parameters. ECG can serve as another screening tool for MASLD in the nonhepatology space.

Antibiotic exposure and depression incidence: A cohort study of the Korean population.

Recent research highlights the crucial role of the gut-brain axis in understanding depression etiologies. While burgeoning studies suggest an association between disruptions in gut microbiota and the development of depression, limited longitudinal studies have investigated this link. To address this gap, we conducted a retrospective cohort study using National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) data in South Korea, involving 199,144 individuals aged 40-79. We examined the impact of cumulative antibiotic exposure (2004-2008) on subsequent depression incidence (2009-2013) by conducting Cox proportional hazards regressions. Our findings show an increasing depression risk with extended antibiotic exposure after adjusting for comorbidities and behavioral covariates. A broader antibiotic spectrum was associated with a higher depression risk. These trends persisted after adjusting for the original antibiotic indications. In conclusion, our study highlights the duration-dependent association between antibiotic exposure and increased depression risk, offering insights into depression etiologies and relevant novel therapeutic tools, and advocating for heightened antibiotic stewardship considering their impact on mental health.

Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study.

BACKGROUND/AIMS: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. METHODS: Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression. RESULTS: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD. CONCLUSION: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.

An artificial intelligence-generated model predicts 90-day survival in alcohol-associated hepatitis: A global cohort study.

BACKGROUND AND AIMS: Alcohol-associated hepatitis (AH) poses significant short-term mortality. Existing prognostic models lack precision for 90-day mortality. Utilizing artificial intelligence in a global cohort, we sought to derive and validate an enhanced prognostic model. APPROACH AND RESULTS: The Global AlcHep initiative, a retrospective study across 23 centers in 12 countries, enrolled patients with AH per National Institute for Alcohol Abuse and Alcoholism criteria. Centers were partitioned into derivation (11 centers, 860 patients) and validation cohorts (12 centers, 859 patients). Focusing on 30 and 90-day postadmission mortality, 3 artificial intelligence algorithms (Random Forest, Gradient Boosting Machines, and eXtreme Gradient Boosting) informed an ensemble model, subsequently refined through Bayesian updating, integrating the derivation cohort's average 90-day mortality with each center's approximate mortality rate to produce posttest probabilities. The ALCoholic Hepatitis Artificial INtelligence Ensemble score integrated age, gender, cirrhosis, and 9 laboratory values, with center-specific mortality rates. Mortality was 18.7% (30 d) and 27.9% (90 d) in the derivation cohort versus 21.7% and 32.5% in the validation cohort. Validation cohort 30 and 90-day AUCs were 0.811 (0.779-0.844) and 0.799 (0.769-0.830), significantly surpassing legacy models like Maddrey's Discriminant Function, Model for End-Stage Liver Disease variations, age-serum bilirubin-international normalized ratio-serum Creatinine score, Glasgow, and modified Glasgow Scores ( p < 0.001). ALCoholic Hepatitis Artificial INtelligence Ensemble score also showcased superior calibration against MELD and its variants. Steroid use improved 30-day survival for those with an ALCoholic Hepatitis Artificial INtelligence Ensemble score > 0.20 in both derivation and validation cohorts. CONCLUSIONS: Harnessing artificial intelligence within a global consortium, we pioneered a scoring system excelling over traditional models for 30 and 90-day AH mortality predictions. Beneficial for clinical trials, steroid therapy, and transplant indications, it's accessible at: https://aihepatology.shinyapps.io/ALCHAIN/ .

Associations of cholecystectomy with metabolic health changes and incident cardiovascular disease: a retrospective cohort study.

Although some studies conducted about the risk of cholecystectomy and cardiovascular disease, there was a limit to explaining the relationship. We investigated the short-term and long-term relationship between cholecystectomy and cardiovascular disease, and evidence using the elements of the metabolic index as an intermediate step. It was a retrospective cohort study and we used the National Health Insurance Service database of South Korea between 2002 and 2015. Finally, 5,210 patients who underwent cholecystectomy and 49,457 at 1:10 age and gender-matched controls of subjects were collected. The main results was estimated by Multivariate Cox proportional hazard regression to calculate the hazard ratio (HR) with 95% confidence interval (CI) for risk of cardiovascular disease after cholecystectomy. Regarding short-term effects of cholecystectomy, increased risk of cardiovascular disease (aHR 1.35, 95% CI 1.15-1.58) and coronary heart disease (aHR 1.77, 95% CI 1.44-2.16) were similarly seen within 2 years of surgery. When analyzing the change in metabolic risk factors, cholecystectomy was associated with a change in systolic blood pressure (adjusted mean [aMean]: 1.51, 95% CI: [- 1.50 to - 4.51]), total cholesterol (aMean - 14.14, [- 20.33 to 7.95]) and body mass index (aMean - 0.13, [- 0.37 to 0.11]). Cholecystectomy patients had elevated risk of cardiovascular disease in the short-term, possibly due to the characteristics of the patient before surgery. The association of cholecystectomy and cardiovascular disease has decreased after 2 years in patients who underwent cholecystectomy, suggesting that because of improvement of metabolic health, cholecystectomy-associated elevation of cardiovascular disease risk may be ameliorated 2 years after cholecystectomy.

Reversal of nonalcoholic fatty liver disease reduces the risk of cardiovascular disease among Korean.

Nonalcoholic fatty liver disease (NAFLD) is considered an independent risk factor for the development of cardiovascular disease. However, the association between changes in NAFLD status and the risk of cardiovascular disease (CVD) remains uncertain. Starting January 1, 2013, participants were followed until the occurrence of CVD event, death, or December 31, 2020. This was a population-based cohort study that included data from adults aged ≥ 20, who underwent 2 consecutive health screenings from 2009 to 2012. NAFLD was defined as a Fatty Liver Index ≥ 60 at each screening. The primary endpoint was a CVD event, which encompassed ischemic heart disease and cerebrovascular disease. The association between changes in NAFLD status and the risk of CVD was determined using multivariable Cox proportional hazards regression. This cohort comprised 4656,305 adults with a median age of 53 years. During 36,396,968 person-years of follow-up, 238,933 (5.1%) CVD events were observed. Compared to patients with no NAFLD at both screenings, patients who developed NAFLD at the second screening exhibited an increased risk of CVD (adjusted hazard ratio, 1.15; 95% confidence interval, 1.13-1.17). In contrast, individuals who recovered from NAFLD at the second screening demonstrated a reduced CVD risk compared to those with persistent NAFLD (adjusted hazard ratio, 0.91; 95% confidence interval, 0.90-0.92). The reversal of NAFLD is associated with a reduced risk of CVD. Therefore, focusing on NAFLD treatment could serve as a clinical target for lowering CVD risk.

MELD 3.0 adequately predicts mortality and renal replacement therapy requirements in patients with alcohol-associated hepatitis.

Background & Aims: Model for End-Stage Liver Disease (MELD) score better predicts mortality in alcohol-associated hepatitis (AH) but could underestimate severity in women and malnourished patients. Using a global cohort, we assessed the ability of the MELD 3.0 score to predict short-term mortality in AH. Methods: This was a retrospective cohort study of patients admitted to hospital with AH from 2009 to 2019. The main outcome was all-cause 30-day mortality. We compared the AUC using DeLong's method and also performed a time-dependent AUC with competing risks analysis. Results: A total of 2,124 patients were included from 28 centres from 10 countries on three continents (median age 47.2 ± 11.2 years, 29.9% women, 71.3% with underlying cirrhosis). The median MELD 3.0 score at admission was 25 (20-33), with an estimated survival of 73.7% at 30 days. The MELD 3.0 score had a better performance in predicting 30-day mortality (AUC:0.761, 95%CI:0.732-0.791) compared with MELD sodium (MELD-Na; AUC: 0.744, 95% CI: 0.713-0.775; p = 0.042) and Maddrey's discriminant function (mDF) (AUC: 0.724, 95% CI: 0.691-0.757; p = 0.013). However, MELD 3.0 did not perform better than traditional MELD (AUC: 0.753, 95% CI: 0.723-0.783; p = 0.300) and Age-Bilirubin-International Normalised Ratio-Creatinine (ABIC) (AUC:0.757, 95% CI: 0.727-0.788; p = 0.765). These results were consistent in competing-risk analysis, where MELD 3.0 (AUC: 0.757, 95% CI: 0.724-0.790) predicted better 30-day mortality compared with MELD-Na (AUC: 0.739, 95% CI: 0.708-0.770; p = 0.028) and mDF (AUC:0.717, 95% CI: 0.687-0.748; p = 0.042). The MELD 3.0 score was significantly better in predicting renal replacement therapy requirements during admission compared with the other scores (AUC: 0.844, 95% CI: 0.805-0.883). Conclusions: MELD 3.0 demonstrated better performance compared with MELD-Na and mDF in predicting 30-day and 90-day mortality, and was the best predictor of renal replacement therapy requirements during admission for AH. However, further prospective studies are needed to validate its extensive use in AH. Impact and implications: Severe AH has high short-term mortality. The establishment of treatments and liver transplantation depends on mortality prediction. We evaluated the performance of the new MELD 3.0 score to predict short-term mortality in AH in a large global cohort. MELD 3.0 performed better in predicting 30- and 90-day mortality compared with MELD-Na and mDF, but was similar to MELD and ABIC scores. MELD 3.0 was the best predictor of renal replacement therapy requirements. Thus, further prospective studies are needed to support the wide use of MELD 3.0 in AH.

Association of post-smoking cessation changes in fasting serum glucose with changes in predicted fatty liver score.

Major post-cessation metabolic changes include weight gain and hyperglycemia. However, the association of post-cessation change in fasting serum glucose (FSG) with risk of fatty liver remains unclear. A total of 111,106 participants aged 40 and above who underwent health screening at least once in two examination periods were extracted from the Korean National Health Insurance Service-National Sample Cohort. Fatty liver status was evaluated using the Korean National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score. Linear and logistic regression were used to calculate the adjusted mean (aMean) and adjusted odds ratio (aOR) with 95% confidence intervals. Compared to stable (aMean 0.10; 95% CI 0.03-0.18) and decline (aMean - 0.60; 95% CI - 0.71 to 0.49) groups, FSG elevation (aMean 1.28; 95% CI 1.16-1.39) was associated with higher K-NAFLD score even within different body mass index change groups. Risk of fatty liver was significantly reduced among participants with stable (aOR 0.38; 95% CI 0.31-0.45) and declined (aOR 0.17; 95% CI 0.13-0.22) FSG levels after smoking cessation compared to FSG elevation group. This study suggests that quitters with elevated FSG are associated with higher NAFLD risk and may benefit from careful monitoring of FSG levels and management of other cardiovascular risk factors.

Disproportionate increases in alcohol-associated hepatitis incidence in women and individuals of low socioeconomic status: A population-based study using the Rochester epidemiology project database.

BACKGROUND: Alcohol-associated hepatitis (AH) is among the deadliest liver diseases, but its incidence is poorly defined. The aim of our study was to define the incidence of AH meeting the National Institute on Alcohol Abuse and Alcoholism criteria and to identify risk factors for AH. METHODS: We conducted a retrospective cohort study using the Rochester epidemiology project database on adult patients hospitalized with AH between January 1, 2000 and December 31, 2018. Patients were screened using ICD-9 codes and then included if they met the National Institute on Alcohol Abuse and Alcoholism criteria on manual chart review. Baseline demographics, comorbidities, access to care, liver-related complications, and outcomes were obtained. The HOUsing-based index of SocioEconomic status index was used to measure socioeconomic status. Incidence rates were calculated in cases per 100,000 person-years of follow-up. RESULTS: Among 204 patients, the cumulative AH incidence was 6.8 per 100,000 person-years. Between 2000-2004 and 2015-2018, AH incidence among males increased from 8.4 to 14.7 per 100,000 py, whereas AH incidence among females increased by 7-fold from 0.8 to 5.9 per 100,000 py. Such increases among females were accompanied by increases in comorbid depression and anxiety. The proportion of patients with AH in the lower socioeconomic status quartiles increased from 62.9% between 2000 and 2004 to 73.3% between 2015 and 2019. CONCLUSIONS: The incidence of AH is increasing rapidly, especially among females and individuals of lower socioeconomic status. There are areas of unmet need in preventative measures and treatments for comorbid psychiatric disorders in patients at high risk of AH.

Association between antibiotics and dementia risk: A retrospective cohort study.

Background: The possible relation between antibiotic exposure and the alteration of gut microbiota, which may affect dementia risk, has been revealed. However, the association between antibiotics and dementia incidence has rarely been studied. We aimed to determine the association between antibiotic exposure and the risk of dementia. Methods: This population-based retrospective cohort study used data from the National Health Insurance Service-Health Screening Cohort (NHIS-HEALS) in South Korea. Exposure was the cumulative days of antibiotic prescription from 2002 to 2005. Newly diagnosed overall dementia, Alzheimer's disease (AD), and vascular dementia (VD) were identified based on diagnostic codes and prescriptions for dementia-related drugs. The follow-up investigation was carried out from 1 January 2006 to 31 December 2013. The Cox proportional hazards regression was used to assess the association between cumulative antibiotic prescription days and dementia incidence. Results: A total of 313,161 participants were analyzed in this study. Compared to antibiotic non-users, the participants who used antibiotics for 91 or more days had an increased risk of overall dementia [adjusted hazard ratio (aHR), 1.44; 95% confidence interval (CI), 1.19-1.74], AD (aHR, 1.46; 95% CI, 1.17-1.81), and VD (aHR, 1.38; 95% CI, 0.83-2.30). Those who used five or more antibiotic classes had higher risks of overall dementia (aHR, 1.28; 95% CI, 1.00-1.66) and AD (aHR, 1.34; 95% CI, 1.00-1.78) than antibiotic non-users. Conclusion: Antibiotic exposure may increase the risk of dementia in a cumulative duration-dependent manner among adult participants. Future studies are needed to assess the causality between the long-term prescription of antibiotics and dementia risk.

Hepatocellular carcinoma surveillance: current practice and future directions.

Hepatocellular carcinoma (HCC) is among the leading causes of cancer incidence and mortality worldwide. Surveillance of individuals with cirrhosis or other conditions that confer a high risk of HCC development is essential for early detection and improved overall survival. Biannual ultrasonography with or without alpha-fetoprotein is widely recommended as the standard method for HCC surveillance, but it has limited sensitivity in early disease and may be inadequate in certain individuals. This review article will provide a comprehensive overview of the current landscape of HCC surveillance, including the rationale and indications for HCC surveillance, standard methods for HCC surveillance, and their strengths/limitations. Alternative surveillance methods such as the role of cross-sectional imaging, emerging circulating biomarkers, as well as the problem of under-utilization of HCC surveillance and surveillance-related harms will also be discussed in this review.

Machine Learning Techniques Differentiate Alcohol-Associated Hepatitis From Acute Cholangitis in Patients With Systemic Inflammation and Elevated Liver Enzymes.

OBJECTIVE: To develop machine learning algorithms (MLAs) that can differentiate patients with acute cholangitis (AC) and alcohol-associated hepatitis (AH) using simple laboratory variables. METHODS: A study was conducted of 459 adult patients admitted to Mayo Clinic, Rochester, with AH (n=265) or AC (n=194) from January 1, 2010, to December 31, 2019. Ten laboratory variables (white blood cell count, hemoglobin, mean corpuscular volume, platelet count, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, albumin) were collected as input variables. Eight supervised MLAs (decision tree, naive Bayes, logistic regression, k-nearest neighbor, support vector machine, artificial neural networks, random forest, gradient boosting) were trained and tested for classification of AC vs AH. External validation was performed with patients with AC (n=213) and AH (n=92) from the MIMIC-III database. A feature selection strategy was used to choose the best 5-variable combination. There were 143 physicians who took an online quiz to distinguish AC from AH using the same 10 laboratory variables alone. RESULTS: The MLAs demonstrated excellent performances with accuracies up to 0.932 and area under the curve (AUC) up to 0.986. In external validation, the MLAs showed comparable accuracy up to 0.909 and AUC up to 0.970. Feature selection in terms of information-theoretic measures was effective, and the choice of the best 5-variable subset produced high performance with an AUC up to 0.994. Physicians did worse, with mean accuracy of 0.790. CONCLUSION: Using a few routine laboratory variables, MLAs can differentiate patients with AC and AH and may serve valuable adjunctive roles in cases of diagnostic uncertainty.

Association between Proton Pump Inhibitor Use and Risk of Hepatocellular Carcinoma: A Korean Nationally Representative Cohort Study.

(1) Background: The association between proton pump inhibitor (PPI) use and hepatocellular carcinoma (HCC) has been controversial, especially in the general population. We aimed to determine the impact of PPI on HCC risk in participants without liver cirrhosis or chronic hepatitis virus infection. (2) Methods: We assessed 406,057 participants from the Korean National Health Insurance Service database who underwent health screening from 2003 to 2006. We evaluated exposure to PPI before the index date using a standardized daily defined dose (DDD) system. The association of proton pump inhibitor use with the risk of HCC was evaluated using multivariable-adjusted Cox proportional hazards regression. (3) Results: Compared with non-users, PPI use was not associated with the HCC risk in low (<30 DDDs; aHR, 1.07; 95% CI, 0.91−1.27), intermediate (30 ≤ PPI < 60 DDDs; aHR, 0.96; 95% CI, 0.73−1.26), and high (≥60 DDDs; aHR, 0.86; 95% CI, 0.63−1.17) PPI groups in the final adjustment model. In addition, risks of cirrhosis-associated HCC and non-cirrhosis-associated HCC were not significantly associated with PPI use. The results remained consistent after excluding events that occurred within 1, 2, and 3 years to exclude pre-existing conditions that may be associated with the development of HCC. We also found no PPI-associated increase in HCC risk among the selected population, such as those with obesity, older age, and chronic liver diseases. (4) Conclusions: PPI use may not be associated with HCC risk regardless of the amount. We call for future studies conducted in other regions to generalize our findings.

Racial and ethnic disparities in early treatment with immunotherapy for advanced HCC in the United States.

BACKGROUND AND AIMS: Immunotherapy has emerged as an effective treatment for patients with advanced-stage HCC. We aimed to investigate the efficacy of immunotherapy for advanced HCC in a nationwide cohort and racial and ethnic disparities in access to immunotherapy. APPROACH AND RESULTS: We used the US National Cancer Database to identify patients with tumor-node-metastasis stage 3 or 4 HCC between 2017 and 2018. We performed multivariable Cox regression to identify factors associated with overall survival (OS) and logistic regression to identify factors associated with receipt of immunotherapy. Of the 3,990 patients treated for advanced HCC, 3,248 (81.4%) patients received chemotherapy and 742 (18.6%) patients received immunotherapy as a first-line treatment. Immunotherapy was associated with improved OS compared with chemotherapy (adjusted HR: 0.76, 95% CI: 0.65-0.88) after adjusting for covariates. There were racial and ethnic disparities in access to immunotherapy, with Hispanic (adjusted OR [aOR]: 0.63, 95% CI: 0.46-0.83) and Black patients (aOR: 0.71, 95% CI: 0.54-0.89) less likely to receive immunotherapy compared with White patients. There was a significant interaction between race-ethnicity and facility type, with higher disparity observed in nonacademic centers (interaction p = 0.004). CONCLUSIONS: Immunotherapy was associated with improved OS compared with chemotherapy in advanced HCC. There are significant disparities in early access to immunotherapy, likely due to differential access to clinical trials and experimental therapies. A comprehensive approach to monitoring and eliminating racial-ethnic disparities in the management of advanced HCC is urgently needed.